EP2456786B2 - Vecteurs lentiviraux pseudotypés avec une glycoprotéine d'enveloppe de virus sindbis - Google Patents
Vecteurs lentiviraux pseudotypés avec une glycoprotéine d'enveloppe de virus sindbis Download PDFInfo
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- EP2456786B2 EP2456786B2 EP10737715.2A EP10737715A EP2456786B2 EP 2456786 B2 EP2456786 B2 EP 2456786B2 EP 10737715 A EP10737715 A EP 10737715A EP 2456786 B2 EP2456786 B2 EP 2456786B2
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Claims (23)
- Particule de vecteur lentiviral comprenant :(a) une enveloppe comprenant(i) une glycoprotéine E2 du virus Sindbis de SEQ ID NO: 1 dans laquelle 160X est absent ou est un acide aminé autre que l'acide glutamique, ou un variant de SEQ ID NO: 1 présentant au moins 80 % d'identité avec SEQ ID NO: 1 et dans lequel 160X est absent ou est un acide aminé autre que l'acide glutamique, capable d'infecter des cellules dendritiques ; où E2 ne fait pas partie d'une protéine de fusion avec E3 du virus Sindbis ; et(b) un génome de vecteur lentiviral comprenant une ou plusieurs séquences d'intérêt.
- Particule de vecteur lentiviral selon la revendication 1, dans laquelle le 160X est absent ou est la glycine, l'alanine, la valine, la leucine ou l'isoleucine, tel que sélectionné parmi la glycine, la valine, la leucine ou l'isoleucine.
- Particule de vecteur lentiviral selon la revendication 1 ou 2, dans laquelle le variant de la glycoprotéine E2 possède au moins un acide aminé altéré afin de réduire sa charge positive nette.
- Particule de vecteur lentiviral selon la revendication 3, dans laquelle le au moins un acide aminé devant être altéré afin de réduire la charge positive nette est choisi parmi la lysine 70, la lysine 76 ou la lysine 159 de SEQ ID NO: 1, et de préférence dans laquelle les substitutions sont indépendamment choisies parmi l'acide glutamique ou l'acide aspartique.
- Particule de vecteur lentiviral selon la revendication 1, dans laquelle la séquence du variant de E2 est les résidus d'acides aminés 66 à 488 de SEQ ID NO: 3, les résidus d'acides aminés 66 à 488 de SEQ ID NO: 4, ou les résidus d'acides aminés 66 à 486 de SEQ ID NO: 5 ; (variants 1, 2 et 3).
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-5, qui est un variant dans lequel la séquence des résidus 71-75 de SEQ ID NO: 1 est inchangée ou possède une ou deux substitutions qui n'affectent pas l'aptitude du variant à infecter des CD, mais n'altèrent pas le nombre d'acides aminés dans cette région.
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-6, dans laquelle la séquence d'intérêt exprime un produit qui est un antigène ou un agent provoquant une maladie ou une cellule pathologique.
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-6, dans laquelle la séquence d'intérêt code pour un antigène spécifique d'une tumeur, facultativement NY-ESO-1, MAGE, MART-1/Melan A, BAGE, RAGE, un antigène d'une lignée de mélanocytes-mélanome, comme gp100, gp75, mda-7, la tyrosinase ou une protéine apparentée à la tyrosinase ; un antigène de carcinome à cellules rénales, 5T4, SM22-alpha, l'anhydrase carbonique I, l'anhydrase carbonique IX (également connue en tant que G250), des facteurs induits par l'hypoxie (facultativement, HIF-1alpha ou HIF-2alpha), le VEGF ou l'antigène membranaire spécifique de la prostate (PSMA), l'antigène spécifique de la prostate (PSA), des phosphatases acides prostatiques, l'antigène épithélial à six domaines transmembranaires de la prostate (STEAP), NKX3.1, des protéines/peptides épitopiques dérivé(e)s de gènes mutés dans des cellules tumorales ou de gènes transcrits à différents taux dans une tumeur par comparaison à des cellules normales, comme l'enzyme télomérase, la survivine, la mésothéline, ras muté, un réarrangement bcr/abl, Her2/neu, p53 muté ou de type sauvage, le cytochrome P450 1B1, des séquences d'intron anormalement exprimées comme la N-acétylglucosaminyltransférase-V ; des réarrangements clonaux de gènes d'immunoglobulines générant des idiotypes uniques dans un myélome ou des lymphomes à cellules B ; des protéines/peptides épitopiques dérivé(e)s de processus oncoviraux, comme les protéines E6 ou E7 du papillomavirus humain ; ou des protéines oncofoetales non mutées avec une expression sélective dans une tumeur, comme l'antigène carcino-embryonnaire ou l'alpha-foetoprotéine.
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-7, dans laquelle la séquence d'intérêt code pour un antigène dérivé d'un virus, comme un antigène du VIH ou du VIS, un polypeptide d'adénovirus, des polypeptides d'alphavirus, des polypeptides de calicivirus, par exemple un antigène de capside de calicivirus, des polypeptides de coronavirus, un polypeptide du virus de la maladie de Carré, un polypeptide du virus Ebola, un polypeptide d'entérovirus, un polypeptide de flavivirus, un polypeptide du virus de l'hépatite (AE), par exemple un antigène de surface ou de noyau de l'hépatite B, ou les glycoprotéines E1 ou E2, des protéines de noyau ou non structurales du virus de l'hépatite C, un polypeptide d'herpèsvirus, par exemple une glycoprotéine du virus herpès simplex ou du virus de la varicelle et du zona, un polypeptide du virus de l'immunodéficience, par exemple l'enveloppe ou la protéase du virus de l'immunodéficience humaine, un polypeptide du virus de la péritonite infectieuse, un polypeptide du virus de la grippe, par exemple l'hémagglutinine, la neuraminidase ou la nucléoprotéine de la grippe A, un polypeptide du virus de la leucémie, un polypeptide du virus de Marburg, un polypeptide d'orthomyxovirus, un polypeptide de papillomavirus, un polypeptide du virus parainfluenza, par exemple l'hémagglutinine/la neuraminidase, un polypeptide de paramyxovirus, un polypeptide de parvovirus, un polypeptide de pestivirus, un polypeptide de picornavirus, par exemple un polypeptide de capside de poliovirus, un polypeptide de poxvirus, par exemple un polypeptide du virus de la vaccine, un polypeptide du virus de la rage, par exemple la glycoprotéine G du virus de la rage, un polypeptide de réovirus, un polypeptide de rétrovirus, ou un polypeptide de rotavirus.
- Composition comprenant une particule de vecteur lentiviral selon l'une quelconque des revendications 1-9, où la composition possède une UI d'au moins 105/ml.
- Système d'encapsidation d'un vecteur lentiviral pour produire une particule de vecteur lentiviral pseudotypée selon l'une quelconque des revendications 1-9, ou la composition selon la revendication 10, comprenant :(i) une première molécule d'acide nucléique codant pour la glycoprotéine E2 du virus Sindbis selon la revendication 1(a)(i), et ;(ii) une deuxième molécule d'acide nucléique codant pour les protéines gag et pol,(iii) une troisième molécule d'acide nucléique codant pour rev ;(iv) un génome de vecteur lentiviral comprenant une séquence d'intérêt ; et(v) une cellule d'encapsidation.
- Système d'encapsidation d'un vecteur lentiviral selon la revendication 11, dans lequel :(a) la protéine pol possède une intégrase non fonctionnelle ; et/ou(b) la protéine pol possède une intégrase non fonctionnelle avec une mutation D64V ; et/ou(c) le génome de vecteur lentiviral est un génome lentiviral incapable d'intégration ; et/ou(d) la cellule d'encapsidation est stablement transformée avec (ii) et (iii) ; et/ou(e) la cellule d'encapsidation est transfectée avec (i) et (iv) .
- Molécule d'acide nucléique isolée comprenant une séquence de nucléotides codant pour la glycoprotéine E2 ou le variant selon la revendication 1(a)(i), ou l'une quelconque des revendications 2-9.
- Molécule d'acide nucléique selon la revendication 13, dans laquelle la protéine est une polyprotéine E3/E2/6K/E1 du virus Sindbis qui est transformée de sorte que la protéine E2 ne fasse pas partie d'une protéine de fusion avec E3 lorsqu'elle est incorporée dans une enveloppe virale.
- Molécule d'acide nucléique selon la revendication 14, dans laquelle la séquence de E3 correspond (a) aux résidus 1-65 de SEQ ID N0: 20, ou (b) à un variant de celle-ci présentant au moins 80 % d'identité de séquence avec les résidus 1-65 de SEQ ID NO: 20,
où les résidus 62-65 sont RSKR (SEQ ID NO: 27), et le variant est capable d'être incorporé dans une enveloppe virale pseudotypée. - Procédé de fabrication d'une particule de vecteur lentiviral selon l'une quelconque des revendications 1-9, ou de la composition selon la revendication 10, qui consiste à cultiver le système d'encapsidation d'un vecteur lentiviral selon la revendication 11.
- Particule lentivirale selon l'une quelconque des revendications 1-9, ou composition selon la revendication 10, dans laquelle le génome de vecteur lentiviral(a) possède une longue répétition terminale (LTR) en 3' inactivée ou capable d'auto-inactivation ; et/ou(b) comprend un élément U3 dépourvu d'au moins l'un parmi : (i) une séquence amplificatrice ; (ii) une boîte TATA, (iii) un site Sp1, (iv) un site NF-kappa B et (v) une séquence polypurine (PPT) ; et/ou(c) comprend la séquence de nucléotides de SEQ ID NO: 21, 22 ou 23 ; et/ou(d) comprend une séquence de nucléotides codant pour un facteur de maturation/stimulation d'une cellule dendritique.
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-9, ou composition selon la revendication 10, destinée à être utilisée dans un procédé de traitement d'un sujet humain ou animal, qui consiste facultativement à délivrer des particules de vecteur lentiviral à des cellules dendritiques ex vivo.
- Particule de vecteur lentiviral selon l'une quelconque des revendications 1-9, ou composition selon la revendication 10, destinée à être utilisée pour induire une réponse immunitaire spécifique à un antigène, facultativement une réponse humorale et/ou une réponse cellulaire.
- Vaccin thérapeutique ou prophylactique comprenant les particules de vecteur lentiviral selon l'une quelconque des revendications 1-9, ou la composition selon la revendication 10, et un excipient pharmaceutiquement acceptable.
- Vaccin thérapeutique ou prophylactique selon la revendication 20, comprenant en outre un adjuvant.
- Vaccin thérapeutique ou prophylactique selon la revendication 21, dans lequel l'adjuvant est un adjuvant ayant la formule (I) :
- Vaccin thérapeutique ou prophylactique selon la revendication 22, dans lequel(a) A1 est un phosphate ou un sel de phosphate et A2 est l'hydrogène, et(b)(i) R1, R3, R5 et R6 sont un groupe alkyle en C11 à C20, et R2 et R4 sont un groupe hydrocarbyle en C12 à C20 ; ou(ii) R1, R3, R5 et R6 sont un groupe alkyle en C11, et R2 et R4 sont un groupe hydrocarbyle en C13 ; ou(iii) R1, R3, R5 et R6 sont un groupe undécyle, et R2 et R4 sont un groupe tridécyle.
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PL10737715T PL2456786T5 (pl) | 2009-07-24 | 2010-07-22 | Wektory lentiwirusowe pseudotypowane glikoproteiną otoczki wirusa sindbis |
DK13194273.2T DK2770061T3 (en) | 2009-07-24 | 2010-07-22 | NON-INTEGRATING LENTIVIRUS VECTORS |
SI201030576T SI2456786T2 (sl) | 2009-07-24 | 2010-07-22 | Lentiviralni vektorji psevdo-tipizirani z glikoproteinom ovojnice virusa Sindbis |
PL13194273T PL2770061T3 (pl) | 2009-07-24 | 2010-07-22 | Wektory lentiwirusowe nieulegające integracji |
MEP-2014-29A ME01720B (me) | 2009-07-24 | 2010-07-22 | Lentiviralni vektori pseudotipizirani sa omotačem od glikobelančevine iz sindbis-virusa |
RS20140158A RS53257B2 (sr) | 2009-07-24 | 2010-07-22 | Lentiviralni vektori pseudotipizirani sa omotačem od glikobelančevine iz sindbis-virusa |
EP13194273.2A EP2770061B1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux non intégrants |
HRP20140327TT HRP20140327T4 (hr) | 2009-07-24 | 2014-04-04 | Lentiviralni vektori pseudotipizirani sa glikoproteinom ovojnice virusa sindbis |
CY20141100265T CY1115020T1 (el) | 2009-07-24 | 2014-04-08 | Λεντιϊικοι φορεις ψευδοτυποποιημενοι με μια γλυκοπρωτεϊνη του φακελου του ιου sindbis |
CY20181101398T CY1121159T1 (el) | 2009-07-24 | 2018-12-27 | Μη-ενσωματουμενοι λεντiϊικοι φορεις |
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US22849109P | 2009-07-24 | 2009-07-24 | |
PCT/US2010/042870 WO2011011584A1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux pseudotypés avec une glycoprotéine denveloppe de virus sindbis |
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EP13194273.2A Division EP2770061B1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux non intégrants |
EP13194273.2A Division-Into EP2770061B1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux non intégrants |
EP13194273.2 Division-Into | 2013-11-25 |
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EP2456786A1 EP2456786A1 (fr) | 2012-05-30 |
EP2456786B1 EP2456786B1 (fr) | 2014-01-08 |
EP2456786B2 true EP2456786B2 (fr) | 2017-04-19 |
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EP13194273.2A Active EP2770061B1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux non intégrants |
EP10737715.2A Active EP2456786B2 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux pseudotypés avec une glycoprotéine d'enveloppe de virus sindbis |
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EP13194273.2A Active EP2770061B1 (fr) | 2009-07-24 | 2010-07-22 | Vecteurs lentiviraux non intégrants |
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US (3) | US20110064763A1 (fr) |
EP (2) | EP2770061B1 (fr) |
JP (4) | JP2013500015A (fr) |
KR (1) | KR101790187B1 (fr) |
CN (1) | CN102482329B (fr) |
AU (1) | AU2010276194B2 (fr) |
BR (1) | BR112012001653A2 (fr) |
CA (1) | CA2768938C (fr) |
CY (1) | CY1121159T1 (fr) |
DK (2) | DK2456786T4 (fr) |
EA (1) | EA032403B1 (fr) |
ES (2) | ES2702274T3 (fr) |
HK (1) | HK1201557A1 (fr) |
HR (2) | HRP20140327T4 (fr) |
HU (1) | HUE043032T2 (fr) |
IL (1) | IL217679A (fr) |
LT (1) | LT2770061T (fr) |
ME (1) | ME01720B (fr) |
MX (1) | MX2012001075A (fr) |
NZ (1) | NZ597804A (fr) |
PL (2) | PL2456786T5 (fr) |
PT (2) | PT2456786E (fr) |
RS (2) | RS58042B1 (fr) |
SG (1) | SG177744A1 (fr) |
SI (2) | SI2456786T2 (fr) |
SM (1) | SMT201400041B (fr) |
TR (1) | TR201819229T4 (fr) |
WO (1) | WO2011011584A1 (fr) |
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